H2S Donors Reverse Age-Related Gastric Malfunction Impaired Due to Fructose-Induced Injury via CBS, CSE, and TST Expression.

OBJECTIVE: Excess of fructose consumption is related to life-treating conditions that affected more than a third of the global population. Therefore, to identify a newer therapeutic strategy for the impact prevention of high fructose injury in age-related malfunctions of the gastric mucosa (GM) in the animal model is important.

METHODS: Adult and aged male rats were divided into control groups (standard diet, SD) and high fructose diet (HFD) groups; acute water immersion restraint stress (WIRS) was induced for evaluation of GM adaptive response and effects of testing the therapeutic potential of H2S-releasing compounds (H2S donors). Histological examination of gastric damage was done on hematoxylin-eosin stained slides. Cystathionine beta-synthase (CBS), Cystathionine gamma-lyase (CSE), and Thiosulfate-dithiol sulfurtransferase (TST) activities and oxidative index were assessed during exogenous administration of H2S donors: sodium hydrosulfide (NaHS) and the novel hybrid H2S-releasing aspirin (ATB-340). The results showed that HFD increased gastric damage in adult and aged rats. HFD-associated malfunction characterized by low activities of H2S key enzymes, inducing increased oxidation. Pretreatment with NaHS, ATB-340 of aged rats in the models of HFD, and WIRS attenuated gastric damage in contrast to vehicle-treated group (p < 0.05). The effect of ATB-340 was characterized by reverse oxidative index and increased CBS, CSE, and TST activities. In conclusion, H2S donors prevent GM age-related malfunctions by enhancement of CBS, CSE, and TST expression against fructose excess injury though reduction of oxidative damage.